Over the past five years our laboratory has been assessing the determinants of response to furosemide in normal man with extrapolation of these data to clinical conditions in which abnormal response to furosemide occurs. So doing allows use of furosemide as a probe of the pathophysiology of the specific disease state, provides insight as to mechanisms of both normal and abnormal response and allows derivation of more rational therapeutic strategy. In the proposed studies we wish to address questions that are direct extensions of our previous work. 1) Is the time course of absorption of furosemide changed in disease states in which resistance occurs? 2) Does handling of orallly administered furosemide change in patients with congestive heart failure as they improve from the decompensated to the compensated state? 3) In patients with resistance to diuretics, does intravenous infusion of furosemide over a several hour period result in greater response than the same dose administered as a bolus dose? 4) In patients with resistance, can abnormalities in the "dose-response" curve to furosemide be attributed to a specific nephron segment? 5) Is furosemide secreted by the gastrointestinal tract as a component of its nonrenal elimination? 6) Can the effect of indomethacin to decrease solute excretion be ascribed to a specific nephron segment in man? 7) What is the interplay of renal solute and water handling in determining urinary PGE2 excretion--implication as to physiologic role of renal prostaglandins?